The Role of Gamma Interferon in the Generation of Human Macrophages Cytotoxic for Entamoeba histolytica trophozoites

Robert A. SalataDepartment of Internal Medicine, Divisions of Clinical Pharmacology, Infectious Diseases, and Geographic Medicine, University of Virginia, Charlottesville, Virginia 22908

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Henry W. MurrayDepartment of Medicine, Division of Infectious Diseases, Cornell University, New York, New York 10021

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Berish Y. RubinNew York Blood Center, New York, New York 10021

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Jonathan I. RavdinDepartment of Internal Medicine, Divisions of Clinical Pharmacology, Infectious Diseases, and Geographic Medicine, University of Virginia, Charlottesville, Virginia 22908

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Upon exposure to Entamoeba histolytica antigen, lymphocytes from patients treated for amebic liver abscess produce lymphokines which activate monocyte-derived macrophages to kill E. histolytica trophozoites. We now demonstrate that gamma interferon (IFN-γ) is produced by these stimulated lymphocytes and is sufficient but not exclusively necessary to activate monocyte-derived macrophage amebicidal activity. Supernatants from mononuclear cells of 7 patients when stimulated with amebic antigen contained more IFN-γ than comparable supernatants derived from control cells (1,862 U/ml vs. 174 U/ml geometric means, P < 0.01); IFN-γ levels were similar in patient and control supernatants following concanavalin A stimulation. Macrophages activated solely by partially purified IFN-γ or recombinant human IFN-γ (300 U/ml) killed 47% of virulent amebae by 6 hr at 37°C. Monocyte-derived macrophages stimulated with lymphokines elicited by amebic antigen or concanavalin A killed 48% and 57% of axenic E. histolytica trophozoites, respectively, over 6 hr at 37°C (P < 0.001 for each compared to control). Macrophages incubated with the identical lymphokines, but in the presence of monoclonal antibody to IFN-γ, were only able to kill 18% and 27% of amebae, respectively, at 6 hr (P < 0.05 to control or when antibody to IFN-γ was not present). If antibody to IFN-γ was added to the stimulating lymphokine, more macrophages died during interaction with amebae (P < 0.05). In summary, IFN-γ has a major but not exclusive role in activating human monocyte-derived macrophages in vitro to kill virulent E. histolytica trophozoites.

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